Linked Life Data

12042306

Source:http://linkedlifedata.com/resource/pubmed/id/12042306

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2002-8-12
pubmed:abstractText
Ntg2p is a DNA N-glycosylase/apurinic or apyrimidinic lyase involved in base excision repair of oxidatively damaged DNA in Saccharomyces cerevisiae. Using a yeast two-hybrid screen and a GST in vitro transcription and translation assay, the mismatch repair (MMR) protein Mlh1p was demonstrated to interact physically with Ntg2p. The Mlh1p binding site maps to amino acids residues 15-40 of Ntg2p. The Ntg2p binding site is localized in the C-terminal end (483-769) of Mlh1p. Overproduction of Ntg2p results in a mutator phenotype with enhanced frameshift reversion frequency, suggesting partial inhibition of the MMR pathway. In contrast, inactivation of NTG2 does not enhance mutagenesis, indicating that Ntg2p is not required for MMR. Site-directed mutagenesis of the Mlh1p binding domain of Ntg2p revealed three amino acids (Ser(24), Tyr(26), Phe(27)) that are absolutely required for Ntg2p-Mlh1p interaction. These residues are part of a motif found in Ntg2p (Arg(23)-Ser(24)-Lys(25)-Tyr(26)-Phe(27)), Exo1p (Arg(444)-Ser(445)-Lys(446)-Phe(447)-Phe(448)), and Sgs1p (Lys(1383)-Ser(1384)-Lys(1385)-Phe(1386)-Phe(1387)). In these three proteins, the motif is part of the domain that interacts with the C-terminal end of Mlh1p. Furthermore, S445A, F447A, and F448A mutants of Exo1p do not bind Mlh1p, but the wild type Exo1p does. Therefore, we propose that the R/K-S-R/K-Y/F-Y/F sequence could define a Mhl1 binding motif. The results also suggest that base excision repair and MMR can cooperate to prevent deleterious effects of oxidative DNA damage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29963-72
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12042306-Adaptor Proteins, Signal Transducing, pubmed-meshheading:12042306-Amino Acid Motifs, pubmed-meshheading:12042306-Amino Acid Sequence, pubmed-meshheading:12042306-Base Sequence, pubmed-meshheading:12042306-Binding Sites, pubmed-meshheading:12042306-DNA Damage, pubmed-meshheading:12042306-DNA Primers, pubmed-meshheading:12042306-DNA Repair, pubmed-meshheading:12042306-DNA-(Apurinic or Apyrimidinic Site) Lyase, pubmed-meshheading:12042306-Fungal Proteins, pubmed-meshheading:12042306-Molecular Sequence Data, pubmed-meshheading:12042306-Mutagenesis, Site-Directed, pubmed-meshheading:12042306-N-Glycosyl Hydrolases, pubmed-meshheading:12042306-Oxidative Stress, pubmed-meshheading:12042306-Protein Binding, pubmed-meshheading:12042306-Saccharomyces cerevisiae, pubmed-meshheading:12042306-Saccharomyces cerevisiae Proteins, pubmed-meshheading:12042306-Sequence Homology, Amino Acid, pubmed-meshheading:12042306-Two-Hybrid System Techniques
pubmed:year
2002
pubmed:articleTitle
Ntg2p, a Saccharomyces cerevisiae DNA N-glycosylase/apurinic or apyrimidinic lyase involved in base excision repair of oxidative DNA damage, interacts with the DNA mismatch repair protein Mlh1p. Identification of a Mlh1p binding motif.
pubmed:affiliation
Commissariat à l'Energie Atomique, Département de Radiobiologie et Radiopathologie, UMR217 CNRS/CEA Radiobiologie Moléculaire et Cellulaire, Fontenay aux Roses 92265, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't